A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors

A Phase 2, Single-center, Single-arm, Open Label Trial of Vismodegib in Patients With Keratocystic Odontogenic Tumors

The purpose of this study is to determine how well a daily dose of 150 mg of Erivedge (vismodegib) reduces Keratocystic odontogenic tumor (KCOT) size, and to evaluate the safety of this dose. Erivedge is FDA-approved for use in adults with a specific type of skin cancer. However, the drug is experimental for patients with KCOT.

This is a single-center, interventional, single-arm, open-label, two-cohort clinical trial. A total of 20 patients will be enrolled (10 with NBCCS-associated KCOT and 10 with sporadic KCOT) over a period of 2 years. This is a 3 year study where each patient will undergo up to 1 year of treatment and up to 2 years of post-treatment follow-up.

All patients will be assessed for safety and efficacy of the study drug GDC-0449 (Vismodegib).

Inclusion Criteria:

• Males and females, 18 years of age and above at the time the informed consent form is signed;
• Able to understand and sign the Informed Consent Form and other necessary paperwork prior to initiation of study procedures;
• Able to communicate with the investigator/study site personnel, understand and comply with the study requirements, and willing to return for specified visits at the appointed time;
• Patients who have received prior treatment for their KCOT and with a diagnosis of recurrent (maxillary or mandibular) sporadic KCOT or NBCCS-associated KCOT (single or multiple);
• Diagnosis of KCOT will be done by past pathology report or by biopsy at the study site, if applicable;
• Willingness to consent to biopsy of the lesion, if needed;
• Willingness to delay excision of the target tumor site, unless evidence of disease progression or lack of drug tolerability;
• Willingness to donate blood for genetic testing;
• For female patients of childbearing potential, agreement to use two acceptable methods of birth control, including one barrier method during the study and 7 months after discontinuation of study drug;
• For males with female partners of childbearing potential, agreement to use a male condom (with spermicide) and to advise their female partners to use an acceptable method of birth control during the study and for 2 months after the discontinuation of the study drug;
• Agreement not to donate blood/blood products during the study and for 7 months after the discontinuation of the study drug;
• For males not to donate sperm products or semen during treatment and for 2 months after the discontinuation of the study drug;
• Able and willing to swallow pill;
• No malabsorption syndrome or other condition that would interfere with enteral absorption;
• At least 4 weeks since last chemotherapy, investigational therapy, radiotherapy or major surgical procedure and recovered from the first study drug administration;
• KCOT measures at least 1 cm in one dimension on pretreatment volumetric CT scan;
• No clinically significant abnormalities with clinical laboratory assessments;

Exclusion Criteria:

• Concurrent anti-tumor therapy;

• Completion of the most recent anti-tumor therapy (including Vismodegib) less than 4 weeks prior to the initiation of treatment (first study drug administration);

• Uncontrolled medical illness;

• Pregnancy or lactation; female patients who are planning to become pregnant for the duration of the study and 7 months post-treatment;

• Inability or unwillingness to swallow capsules;

• Any medical or psychological illness or condition preventing adequate consent;

• History of significant atherosclerotic disease, including the following:

  • Coronary artery disease (i.e., myocardial infarction within the past year or unstable angina);
  • Documented carotid atheroma;

• Known HIV infection;

• Current alcohol abuse;

• History of resistance to vismodegib (patients who previous received vismodegib for BCC and had no clinical response will be excluded).